A test of the androgen responsiveness of circulating tumor cells in men with metastatic prostate cancer (PCa) before and after androgen-deprivation therapy may help determine the best subsequent treatment, according to a study published online in Cancer Discovery.
David T. Miyamoto, MD, PhD, of the Massachusetts General Hospital Cancer Center in Charlestown, and colleagues measured androgen receptor signaling in circulating tumor cells from 25 men with metastatic PCa before and after treatment.
The researchers found that androgen receptor signaling was predominantly on in untreated patients, while signaling was heterogeneous (androgen receptor-on, androgen receptor-off, and androgen receptor-mixed) in treated patients with castration-resistant PCa. First-line androgen deprivation therapy led to a profound switch in signaling from on to off, while secondary treatment in castration-resistant cancer led to various responses. Patients whose tumor androgen receptor signaling remained on or partially on despite treatment with abiraterone acetate had worse treatment outcomes.
“Acquired resistance to first-line hormonal therapy in prostate cancer is heterogeneous in the extent of androgen receptor pathway reactivation,” Miyamoto and colleagues concluded. “Measurement of pre- and post-treatment androgen receptor signaling within circulating tumor cells may help target such treatments to patients most likely to respond to second-line therapies.”